Balla A, Koneru R, Smiley J, Sershen H, Javitt D C
Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
Neuropsychopharmacology. 2001 Aug;25(2):157-64. doi: 10.1016/S0893-133X(01)00230-5.
Functional dopaminergic hyperactivity is a key feature of schizophrenia. Recent in vivo imaging studies have demonstrated greater striatal dopamine release in response to amphetamine challenge in schizophrenia subjects than in normal controls. N-methyl-D-aspartate (NMDA) receptors are known to play a prominent role in regulation of striatal dopamine release. In humans, NMDA antagonists induce a psychotic state that closely resembles schizophrenia. The present study investigates the degree to which chronic continuous administration of the NMDA antagonist phencyclidine (PCP) induces schizophrenia-like hyperreactivity of striatal dopamine release to amphetamine in rodents. Rats were treated with 10 or 15 mg/kg/d PCP for two weeks by osmotic minipump, and striatal dopamine release to amphetamine challenge (1 mg/kg) was monitored by microdialysis. PCP-treated rats showed significant enhancement in amphetamine-induced dopamine release, along with significantly enhanced locomotor activity. These findings support the concept that NMDA receptor dysfunction may contribute to dopaminergic dysfunction in schizophrenia.
功能性多巴胺能亢进是精神分裂症的关键特征。最近的体内成像研究表明，与正常对照组相比，精神分裂症患者在接受苯丙胺激发后纹状体多巴胺释放量更多。已知N-甲基-D-天冬氨酸（NMDA）受体在调节纹状体多巴胺释放中起重要作用。在人类中，NMDA拮抗剂会诱发一种与精神分裂症极为相似的精神病状态。本研究调查了长期连续给予NMDA拮抗剂苯环利定（PCP）在多大程度上会诱导啮齿动物纹状体多巴胺释放对苯丙胺产生类似精神分裂症的高反应性。通过渗透微型泵给大鼠连续两周注射10或15mg/kg/d的PCP，并用微透析法监测纹状体多巴胺对苯丙胺激发（1mg/kg）的释放情况。接受PCP治疗的大鼠在苯丙胺诱导的多巴胺释放方面显著增强，同时运动活性也显著增强。这些发现支持了NMDA受体功能障碍可能导致精神分裂症中多巴胺能功能障碍这一观点。
